PREDICTION OF BI-STABLE ALTERNATIVE RNA STRUCTURES REVEALS RIBO-REGULATORS THAT FUNCTION VIA CONDITIONAL TRANSCRIPTION TERMINATION IN BACTERIA

RNA cis-regulatory elements, such as riboswitches, play a significant role in gene expression regulation in bacteria. These elements are transcribed upstream to a gene and control its expression by sensing a certain metabolite in the cell. Upon binding the metabolite, the riboswitch changes its structure leading to alteration of the expression of the downstream genes. Many riboswitches work via generating a conditional transcriptional terminator structure upon metabolite binding. We developed a new computational method for the discovery of riboswitches by looking for the two alternative conformations that the molecule takes: one conformation that contains an intrinsic transcription terminator and a different conformation that contains an anti-terminator that can prevent the formation of the terminator. We show that combining this type of computational search with experimental RNA-seq data accurately identified known riboswitches and yields a large number of candidate new ribo-regulators.